Journal of Computer-Aided Molecular Design

, Volume 15, Issue 3, pp 247–258

An improved nicotinic pharmacophore and a stereoselective CoMFA-model for nicotinic agonists acting at the central nicotinic acetylcholine receptors labelled by [3H]-N-methylcarbamylcholine


  • Janne E. Tønder
    • Health Care DiscoveryNovo Nordisk A/S
  • Preben H. Olesen
    • Health Care DiscoveryNovo Nordisk A/S
  • John Bondo Hansen
    • Health Care DiscoveryNovo Nordisk A/S
  • Mikael Begtrup
    • Department of Medicinal ChemistryRoyal Danish School of Pharmacy
  • Ingrid Pettersson
    • Health Care DiscoveryNovo Nordisk A/S

DOI: 10.1023/A:1008140021426

Cite this article as:
Tønder, J.E., Olesen, P.H., Hansen, J.B. et al. J Comput Aided Mol Des (2001) 15: 247. doi:10.1023/A:1008140021426


A study of a series of compounds with agonistic effect at the α4β2 nicotinic acetylcholine receptors resulted in an improved pharmacophore model as well as a CoMFA model. The pharmacophore was composed of three pharmacophoric elements: (1) a site point (a) corresponding to a protonated nitrogen atom, (2) a site point (b) corresponding to an electronegative atom capable of forming a hydrogen bond, and (3) the centre of a heteroaromatic ring or a C=O bond (c). The pharmacophoric elements were related by the following parameters: (a–b) 7.3–8.0 Å, (a–c) 6.5–7.4 Å, and the angle between the two distance vectors (Δbac) 30.4–35.8°. In addition to this, a stereoselective CoMFA model was developed, which showed good predictability even for compound classes not present in the training set.

CoMFA model3D-QSARnicotinic agonistspharmacophore model

Copyright information

© Kluwer Academic Publishers 2001